(Circulation. 1998;98:2180-2186.)
© 1998 American Heart Association, Inc.
Basic Science Reports |
Additive Effects of Hyperinsulinemia and Ischemia on Myocardial GLUT1 and GLUT4 Translocation In Vivo
Presented in part at the 69th Scientific Sessions of the American Heart Association, New Orleans, La, November 11–14, 1996, and published in abstract form (Circulation. 1996;94[suppl I]:I-308).
From the Section of Cardiovascular Medicine (R.R.R., Y.R., X.H., A.J.S., L.H.Y.), Department of Cellular and Molecular Physiology (M.J.C.), and Howard Hughes Medical Institute (G.I.S.), Yale University School of Medicine, New Haven, Conn; and the Department of Metabolic Diseases, Bristol-Myers Squibb, Princeton, NJ (J.R.).
Correspondence to Lawrence H. Young, MD, Section of Cardiovascular Medicine, Yale University School of Medicine, 333 Cedar St, FMP 323, New Haven, CT 05620-8017. E-mail lawrence.young{at}qm.yale.edu
Background—Myocardial ischemia increases glucose uptake through the translocation of GLUT1 and GLUT4 from an intracellular compartment to the sarcolemma. The present study was performed to determine whether hyperinsulinemia causes translocation of myocardial GLUT1 as well as GLUT4 in vivo and whether there are additive effects of insulin and ischemia on GLUT1 and GLUT4 translocation.
Methods and Results—Myocardial glucose uptake and transporter distribution were assessed by arteriovenous measurements, cell fractionation, and immunofluorescence. In fasted anesthetized dogs, hyperinsulinemia increased myocardial glucose extraction 3-fold (P<0.01) and the sarcolemmal content of GLUT4 by 90% and GLUT1 by 50% (P<0.05 for both) compared with saline infusion. In subsequent experiments, glucose uptake and transporter distribution were determined in ischemic and nonischemic regions of hearts from hyperinsulinemic animals during regional myocardial ischemia. Glucose uptake was 50% greater in the ischemic region (P<0.05). This was associated with a 20% increase in sarcolemmal GLUT1 and a 60% increase in sarcolemmal GLUT4 contents in the ischemic region (P<0.05 for both).
Conclusions—Insulin stimulates myocardial glucose utilization through translocation of GLUT1 as well as GLUT4. Insulin and ischemia have additive effects to increase in vivo glucose utilization and augment glucose transporter translocation. We conclude that recruitment of both GLUT1 and GLUT4 contributes to increased myocardial glucose uptake during moderate reductions in coronary blood flow under insulin-stimulated conditions.
Key Words: glucose • insulin • ischemia • metabolism
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